UW scientists believe their at-home test could help more people on anticoagulants monitor their clotting levels and avoid blood clots
In a proof-of-concept study,researchers at the University of Washington (UW) are developing a new smartphone-based technology/application designed to enable people on anticoagulants such as warfarin to monitor their clotting levels from the comfort of their homes. Should this new test methodology prove successful, clinical laboratories may have yet one more source of competition from this at-home PT/INR test solution.
PT/INR (prothrombin time with an international normalized ratio) is one of the most frequently performed clinical laboratory blood tests. This well-proven assay helps physicians monitor clotting in patients taking certain anticoagulation medications.
However, the process can be onerous for those on anticoagulation drugs. Users of this type of medication must have their blood tested regularly—typically by a clinical laboratory—to ensure the medication is working effectively. When not, a doctor visit is required to adjust the amount of the medication in the bloodstream.
Alternatively, where a state’s scope of practice law permits, pharmacists can perform a point-of-care test for the patient, thus allowing the pharmacist to appropriately adjust the patient’s prescription.
Though in the early stages of its development, were the UW’s new smartphone-based blood clotting test to be cleared by the federal Food and Drug Administration (FDA), then users would only need to see a doctor when their readings went and stayed out of range, according to Clinical Lab Products (CLP).
Enabling Patients to Test Their Blood More Frequently
More than eight million Americans with mechanical heart valves or other cardiac conditions take anticoagulants, and 55% of people taking those medication say they fear experiencing life-threatening bleeding, according to the National Blood Clot Alliance.
They have reason to be worried. Even when taking an anticoagulation drug, its level may not stay within therapeutic range due to the effects of food and other medications, experts say.
“In the US, most people are only in what we call the ‘desirable range’ of PT/INR levels about 64% of the time. This number is even lower—only about 40% of the time—in countries such as India or Uganda, where there is less frequent testing. We need to make it easier for people to test more frequently,” said anesthesiologist and co-author of the study Kelly Michaelsen, MD, PhD, UW Assistant Professor of Anesthesiology and Pain Medicine, in a UW news release.
“Back in the day, doctors used to manually rock tubes of blood back and forth to monitor how long it took a clot to form. This, however, requires a lot of blood, making it infeasible to use in home settings,” said senior study author Shyam Gollakota, PhD (above), professor and head of the Networks and Mobile Systems Lab at UW’s Paul G. Allen School of Computer Science and Engineering, in the UW news release. “The creative leap we make here is that we’re showing that by using the vibration motor on a smartphone, our algorithms can do the same thing, except with a single drop of blood. And we get accuracy similar to the best commercially available techniques [used by clinical laboratories].” (Photo copyright: University of Washington.)
How UW’s Smartphone-based Blood Clotting Test Works
The UW researchers were motived by the success of home continuous glucose monitors, which enable diabetics to continually track their blood glucose levels.
According to the Nature Communications paper, here’s how UW’s “smartphone-based micro-mechanical clot detection system” works:
Samples of blood plasma and whole blood are placed into a thimble-size plastic cup.
The cup includes a small copper particle and thromboplastin activator.
When the smartphone is turned on and vibrating, the cup (which is mounted on an attachment) moves beneath the phone’s camera.
Video analytic algorithms running on the smartphone track the motion of the copper particle.
If blood clots, the “viscous mixture” slows and stops.
PT/INR values can be determined in less than a minute.
“Our system visually tracks the micro-mechanical movements of a small copper particle in a cup with either a single drop of whole blood or plasma and the addition of activators,” the researchers wrote in Nature Communications. “As the blood clots, it forms a network that tightens. And in that process, the particle goes from happily bouncing around to no longer moving,” Michaelsen explained.
The system produced these results:
140 de-identified plasma samples: PT/INR with inter-class correlation coefficients of 0.963 and 0.966.
79 de-identified whole blood samples: 0.974 for both PT/INR.
Another At-home Test That Could Impact Clinical Laboratories
The UW scientists intend to test the system with patients in their homes, and in areas and countries with limited testing resources, Medical Device Network reported.
Should UW’s smartphone-based blood-clotting test be cleared by the FDA, there could be a ready market for it. But it will need to be offered it at a price competitive with current clinical laboratory assays for blood clotting, as well as with the current point-of-care tests in use today.
Nevertheless, UW’s work is the latest example of a self-testing methodology that could become a new competitor for clinical laboratories. This may motivate medical laboratories to keep PT/INR testing costs low, while also reporting quick and accurate results to physicians and patients on anticoagulants.
Alternatively, innovative clinical laboratories could develop a patient management service to oversee a patient’s self-testing at home and coordinate delivery of the results with the patient’s physician and pharmacist. This approach would enable the lab to add value for which it could be reimbursed.
Defense attorneys attempted to describe Balwani as simply an investor in Theranos, but prosecutors used the defendant’s own text messages to debunk that claim
Clinical laboratory directors and pathologists following the criminal fraud trial of ex-Theranos President and COO Ramesh “Sunny” Balwani may be experiencing a case of déjà vu as the former executive of the now-defunct blood-testing company has his day in court.
Even as Balwani’s defense team attempted to distance their client from the company’s day-to-day decision-making activities, prosecutors followed an almost identical script from the previous fraud trial of Theranos founder Elizabeth Holmes conducted earlier this year. That trial led to her conviction on four counts of defrauding investors.
As was the case in the Holmes trial, text messages between the two Theranos top executives (Balwani and Holmes) are again center stage in the San Jose, Calif., courtroom of U.S. District Judge Edward Davila.
Balwani Texts Reveal an ‘Unhappy’ Man Under Pressure
Balwani, 56, worked alongside Holmes at Theranos from 2009 to 2016. He purchased $5 million in stock in the company and helped finance the startup by underwriting a $13 million loan. Like Holmes, Balwani faces a dozen counts of fraud and conspiracy to commit wire fraud.
Jurors in the Balwani trial were shown a collection of private text messages between Balwani and Holmes—who also was his girlfriend at the time—that shed light on their business and personal relationships.
“I am responsible for everything at Theranos,” Balwani wrote in a text exchange with Holmes, NBC Bay Area reported. “I worked six years day and night to help you … sad about where we are,” he wrote.
“I am very unhappy because my work sucks,” Balwani told Holmes in another text. NBC Bay Area also reported on other text messages that discussed meeting new investors, meeting revenue goals, and potentially buying a corporate plane.
Just like former Theranos CEO/founder Elizabeth Holmes, former Theranos president/COO Ramesh “Sunny” Balwani (above) faces a dozen counts of fraud and conspiracy to commit wire fraud. Clinical laboratory directors will be particularly interested in the outcome of these trails since the responsibility of CLIA-laboratory directors to report anomalies in medical laboratory testing played a key part in defense testimony. (Photo copyright: The Guardian.)
Defense Counterattacks with Expert Testimony
Balwani’s defense team launched a counterattack the following day when witness Constance Cullen, PhD, a former immunologist at Schering-Plough, stated on cross examination that she dealt only with Holmes and never met Balwani or other Theranos executives, NBC Bay Area reported.
During Holmes’ trial, Cullen testified that Holmes had used the Schering-Plough logo without authorization on studies presented to potential investors which aimed to validate Theranos’ blood-testing technology.
Balwani’s defense team previously described him as a Theranos “shareholder” in an effort to distance him from executive decisions that allegedly misled Theranos investors about the startup’s revenues and accuracy of the company’s “revolutionary” Edison blood-testing device, which Theranos claimed could perform hundreds of clinical laboratory tests using a finger-prick of blood.
According to additional NBC Bay Area coverage of the trial, a former Walgreens executive testified he worked closely with Balwani during the drugstore chain’s failed multiyear partnership with Theranos, which included a $50 million investment to bring in-store medical laboratory testing to its pharmacies.
“As a person who was an investor and essentially serving as the chief operations officer, Sunny Balwani absolutely was intimately involved in the Walgreens relationship and all the relationships Theranos had,” chief legal analyst for Esquire Digital and editor of Today’s Esquire, Aron Solomon, JD, told NBC Bay Area in a video interview.
NBC Bay Area reported that prosecutors introduced text messages between Balwani and Holmes in which Balwani admitted he did not inform Walgreens that third-party equipment—not the Theranos Edison device—was being used for much of the actual clinical laboratory testing done in Walgreens stores.
Prosecutors Claim Balwani, Holmes Worked ‘Together’ to Defraud Investors
Earlier in April, government lawyers responded to claims from Holmes’ defense team that Judge Davila should set aside the convictions in Holmes’ fraud case because evidence at trial did not support a guilty verdict, Fortune reported.
The prosecutors countered in a court filing that the “overwhelming weight of the evidence admitted at trial supports the jury’s conviction” of conspiracy to commit wire fraud and fraud on Theranos investors.
Prosecutors maintained the Holmes trial was “replete with examples” of Holmes and Balwani “working together and conspiring to effectuate a scheme to defraud investors.” The two “were constantly in communication via email, text message, and in-person meetings” about the company’s laboratories, financials, patient blood-testing, and relationships with Walgreens, investors, and visits by regulators, the Fortune article noted.
Holmes was convicted on January 3, 2022, on three counts of wire fraud and one count of conspiracy to commit wire fraud. Her sentencing date is September 26. She faces up to 20 years in prison but remains free on bond while awaiting sentencing. Balwani’s trial is ongoing.
Clinical laboratory managers and pathologists following the Theranos saga with interest should expect more revelations in the weeks to come. Balwani’s trial, which began in March, is expected to last at least three months.
Labcorp, the commercial laboratory giant headquartered in Burlington, N.C., has billions of diagnostic test results archived. It takes samplings of those results and runs them through a machine learning algorithm that compares the data against a condition of interest, such as chronic kidney disease (CKD). Machine learning is a subdiscipline of AI.
Based on patterns it identifies, the machine learning algorithm can predict future test results for CKD based on patients’ testing histories, explained Stan Letovsky, PhD, Vice President for AI, Data Sciences, and Bioinformatics at Labcorp. Labcorp has found the accuracy of those predictions to be better than 90%, he added.
Labcorp also has created an AI-powered dashboard that—once layered over an electronic health record (EHR) system—allows physicians to configure views of an individual patient’s existing health data and add a predictive view based on the machine learning results.
For anatomic pathologists, this type of setup can quickly bring a trove of data into their hands, allowing them to be more efficient with patient diagnoses. The long-term implications of using this technology are significant for pathology groups’ bottom line.
Stan Letovsky, PhD (above), Vice President for AI, Data Sciences, and Bioinformatics at Labcorp, discussed AI developments in digital pathology during his keynote address at the 2022 Executive War College in New Orleans. “The best thing as a community that we can do for patients and their physicians with AI is to identify care gaps early on,” he said, adding, “If pathologists want to grow and improve their revenue, they have to be more productive.” (Photo copyright: Dark Intelligence Group).
Mayo Clinic Plans to Digitize 25 Million Glass Slides
In other AI developments, Mayo Clinic in Rochester, Minn., has started a project to digitally scan 25 million tissue samples on glass slides—some more than 100 years old. As part of the initiative, Mayo wants to digitize five million of those slides within three years and put them on the cloud, said pathologist and physician scientist Jason Hipp, MD, PhD, Chair of Computational Pathology and AI at Mayo Clinic.
“We want to be a hub within Mayo Clinic for digital pathology,” Hipp told Executive War College attendees during his keynote address.
Hipp views his team as the bridge between pathologists and the data science engineers who develop AI algorithms. Both sides must collaborate to move AI forward, he commented, yet most clinical laboratories and pathology groups have not yet developed those relationships.
“We want to embed both sides,” Hipp added. “We need the data scientists working with the pathologists side by side. That practical part is missing today.”
The future medical laboratory at Mayo Clinic will feature an intersection of pathology, computer technology, and patient data. Cloud storage is a big part of that vision.
“AI requires storage and lots of data to be practical,” Hipp said.
Drone program will enable delivery of medical laboratory samples during the day, rather than just at night, allowing daytime sample processing that will increase efficiency and shorten time to results
Healthcare network clinical laboratories continue to explore the use of unmanned aerial vehicles (UAVs), commonly known as drones, to safely deliver medical supplies and clinical laboratory specimens between locations. Dark Daily has covered several similar pioneering drone programs taking place around the world in recent years.
The latest medical laboratory company to launch a drone delivery program is Interpath Laboratory, an independent full-service medical laboratory in the Pacific Northwest.
In partnership with Arizona-based Spright—the drone division of Air Methods, a patient transport company with 300 bases in 48 states—Interpath recently announced the launch of its drone delivery pilot program for delivering lab testing specimens from Yellowhawk Tribal Health Center to Interpath’s medical laboratory in Pendleton, Oregon.
The two organizations hope the initiative will expedite the turnaround time needed for test results, thus allowing for timelier diagnoses and improving patient care and outcomes.
“Many communities located in remote or rural areas lack timely and convenient access to essential medical supplies and service,” said Joe Resnik (above), president of Spright in a press release. “We look forward to this proof-of-concept, showcasing drone delivery’s ability to solve many of healthcare’s existing access and efficiency challenges, while also improving patient care and experience.” (Photo copyright: KVS Technologies.)
Replacing Automobile-based Medical Laboratory Specimen Delivery
“If this pilot program is successful and we are able to utilize this service, our patients have the opportunity to benefit from more rapid test results and access follow-up medical procedures and services,” stated Aaron Hines, CEO of Yellowhawk Tribal Health Center in a press release. “This project could help us further our mission of providing high-quality, primary healthcare for the Confederated Tribes of the Umatilla Indian Reservation (CTUIR).”
Currently, patient samples taken throughout the day at various Yellowhawk facilities are picked up and delivered to Interpath’s clinical laboratory in the evening via gasoline-powered vehicles. A successful drone service would allow lab test specimens to be repeatedly picked up and delivered to the lab for analysis throughout the day.
“Medical laboratory services in rural areas frequently must invest intensive time and resources into sample pick-up,” said Tom Kennedy, president of Interpath Laboratory, in the press release. “We anticipate Spright’s drone delivery service will alleviate many of the drawbacks and costs associated with automobile-based delivery. This initiative represents an example of our embrace of innovative solutions that provide more efficient and effective services to our clients.”
In February, Spright held test flights that transported clinical laboratory specimens from Yellowhawk Tribal Health Center to Interpath’s main medical laboratory in Pendleton, Ore. The 15-mile flight used a Wingcopter 198 drone (above) which employs beyond-visual-line-of-sight (BVLOS) technology. Manufactured in Germany, the Wingcopter 198 has a wingspan of five feet ten inches and can carry up to 13 pounds. It has a range of 46 to 68 miles, and a maximum speed of approximately 62 to 90 miles per hour, depending on the weight of its load. (Photo copyright: sUAS News.)
Other Clinical Laboratory Drone Deliver Programs Worldwide
Innovative approaches, such as the utilization of drones to make clinical laboratory specimen deliveries, can help circumvent many of the challenges in delivering healthcare to rural areas. But UAV delivery networks work equally well for faster specimen transferals in urban environments as well, leading to timelier diagnoses of diseases and ultimately to better patient outcomes.
Should the test prove clinically viable, it could lead to new biomarkers for eye disease diagnostics and a new assay for clinical laboratories
Scientists at Flinders University in Australia have developed a genetic blood or saliva test that, they say, is 15 times more effective at identifying individuals at high risk of glaucoma than current medical laboratory tests.
If so, this discovery could lead to new biomarkers for diagnostic blood tests that help medical professionals identify and treat various diseases of the eye. Their test also can be performed on saliva samples. The researchers plan to launch a company later in 2022 to generate an accredited test that can be used in clinical trials.
“Early diagnosis of glaucoma can lead to vision-saving treatment, and genetic information can potentially give us an edge in making early diagnoses, and better treatment decisions,” said lead researcher Owen Siggs, PhD, Associate Professor, College of Medicine and Public Health at Flinders University, in a university press release.
Flinders University researchers have been collaborating with scientists at the QIMR Berghofer Medical Research Institute and other research institutes worldwide for some time to identify genetic risk factors for glaucoma, the press release noted.
“In the cross-sectional study of monogenic and polygenic variants related to the disease, the new genetic test was evaluated in 2,507 glaucoma patients in Australia and 411,337 people with or without glaucoma in the UK. The test, conducted using a blood or saliva sample, could potentially detect individuals at increased risk before irreversible vision loss happens,” Medical Device Network reported.
“Genetic testing is not currently a routine part of glaucoma diagnosis and care, but this test has the potential to change that,” said Jamie Craig, PhD, (above), Distinguished Professor, College of Medicine and Health at Flinders University in Australia and senior author of the study, in a press release. “We’re now in a strong position to start testing this in clinical trials,” he added. This is yet another example of how new research is identifying a novel biomarker that could be incorporated into a clinical laboratory test. (Photo copyright: Flinders University.)
Who Is at Risk for Glaucoma?
Glaucoma is a group of eye diseases that are typically caused by a buildup of pressure within the eye. The eyeball contains and produces a fluid called aqueous humour which provides nutrition to the eye and keeps the eye in a proper pressurized state. Any excess of this fluid should be automatically released via a drainage canal called the trabecular meshwork.
But that’s not always the case. When the fluid cannot drain properly, intraocular pressure is created. Most forms of glaucoma are characterized by this pressure, which can damage the optic nerve and eventually cause vision loss and even blindness. Treatments for the disease include medications, laser treatments, and surgery.
Anyone can develop glaucoma, but according to the Mayo Clinic, individuals at higher risk of the disease include:
Individuals over the age of 60.
Those with a family history of glaucoma.
People of African, Asian, or Hispanic descent.
Patients with certain medical conditions, such as diabetes, heart disease, high blood pressure, and sickle cell anemia.
Those with corneas that are thin in the center.
Individuals who have had a past eye injury or certain types of eye surgery.
People who have taken corticosteroid medications, especially eyedrops, for an extended period of time.
Glaucoma is the second leading cause of blindness worldwide, particularly among the elderly. When diagnosed early, the condition is manageable, but even with treatment, about 15% of glaucoma patients become blind in at least one eye within 20 years.
According to the federal Centers for Disease Control and Prevention (CDC), approximately three million Americans are living with glaucoma. The disease often has no early symptoms, which is why it is estimated that about 50% of individuals who have glaucoma do not realize they have the illness.
Thus, a clinically-viable genetic test that is 15 times more likely to identify people at risk for developing glaucoma in its early stages would be a boon for ophthalmology practices worldwide and could save thousands from going blind.
More research and clinical trials are needed before the Flinders University genetic test for glaucoma becomes available. But the discovery alone demonstrates the importance of continuing research into identifying novel biomarkers that could be incorporated into useful clinical laboratory diagnostic tests.
Many of the mutations were found at sites on the spike protein where antibodies bind, which may explain why the Omicron variant is more infectious than previous variants
Scientists at the University of Missouri (UM) now have a better understanding of why the SARS-CoV-2 Omicron variant is more infectious than previous variants and that knowledge may lead to improved antivirals and clinical laboratory tests for COVID-19.
As the Omicron variant of the coronavirus spread across the globe, scientists noted it appeared to be more contagious than previous variants and seemed resistant to the existing vaccines. As time went by it also appeared to increase risk for reinfection.
The UM researchers wanted to know why. They began by examining the Omicron variant’s mutation distribution, its evolutionary relationship to previous COVID-19 variants, and the structural impact of its mutations on antibody binding. They then analyzed protein sequences of Omicron variant samples collected from around the world.
“We know that viruses evolve over time and acquire mutations, so when we first heard of the new Omicron variant, we wanted to identify the mutations specific to this variant,” said Kamlendra Singh, PhD, Associate Research Professor, Department of Veterinary Pathobiology at UM’s College of Veterinary Medicine (CVM), in a UM press release.
Kamlendra Singh, PhD (above), an associate research professor in the Department of Veterinary Pathobiology at UM’s College of Veterinary Medicine, led the team that identified 46 mutations of the SARS-CoV-2 Omicron variant. “I went to India last April and I got infected by the Delta variant. So, it then became personal to me,” he told NBC affiliate KOMU. The UM team hopes their findings lead to improvements in existing COVID-19 antivirals and clinical laboratory tests. (Photo copyright: University of Missouri.)
In their paper, the UM team wrote, “Here we present the analyses of mutation distribution, the evolutionary relationship of Omicron with previous variants, and probable structural impact of mutations on antibody binding. … The structural analyses showed that several mutations are localized to the region of the S protein [coronavirus spike protein] that is the major target of antibodies, suggesting that the mutations in the Omicron variant may affect the binding affinities of antibodies to the S protein.”
There are a total of 46 highly prevalent mutations throughout the Omicron variant.
Twenty-three of the 46 mutations belong to the S protein (more than any previous variant).
Twenty-three of 46 is a markedly higher number of S protein mutations than reported for any SARS-CoV-2 variant.
A significant number of Omicron mutations are at the antibody binding surface of the S protein.
“Mutation is change in the genome that results in a different type of protein,” Singh told NBC affiliate KOMU. “Once you have different kinds of protein after the virus and the virus attacks the cell, our antibodies do not recognize that, because it has already been mutated.”
Omicron Mutations Interfere with Antibody Binding
Of the 46 Omicron variant mutations discovered by the UM researchers, some were found in areas of the coronavirus’ spike protein where antibodies normally bind to prevent infection or reinfection.
“The purpose of antibodies is to recognize the virus and stop the binding, which prevents infection,” Singh explained. “However, we found many of the mutations in the Omicron variant are located right where the antibodies are supposed to bind, so we are showing how the virus continues to evolve in a way that it can potentially escape or evade the existing antibodies, and therefore continue to infect so many people.”
These findings explain how the Omicron variant bypasses pre-existing antibodies in a person’s blood to cause initial infection as well as reinfection.
The UM team hopes their research will help other scientists better understand how the SARS-CoV-2 coronavirus has evolved and lead to future clinical laboratory antiviral treatments.
“The first step toward solving a problem is getting a better understanding of the specific problem in the first place,” Singh said. “It feels good to be contributing to research that is helping out with the pandemic situation, which has obviously been affecting people all over the world.”
Singh and his team have developed a supplement called CoroQuil-Zn designed to reduce a patient’s viral load after being infected with the SARS-CoV-2 coronavirus. The drug is currently being used in parts of India and is awaiting approval from the US Food and Drug Administration (FDA).
New discoveries about SARS-CoV-2 and its variants continue to further understanding of the coronavirus. Research such as that performed at the University of Missouri may lead to new clinical laboratory tests, more effective treatments, and improved vaccines that could save thousands of lives worldwide.
